Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals: The Hisayama Study

Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals: The Hisayama Study
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DOI:
10.1111/jdi.13232
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发表时间:
2020-03-10
影响因子:
3.2
通讯作者:
Ninomiya, Toshiharu
Ninomiya, Toshiharu
中科院分区:
医学3区
文献类型:
--
作者:
Inaishi, Jun;Saisho, Yoshifumi;Ninomiya, Toshiharu

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目的/导言:葡萄糖耐受不良发生过程中组织学定量β-和α-细胞质量的变化尚未完全阐明。本研究的目的是根据葡萄糖耐量状态探索β-和α-细胞质量的差异。材料和方法:共103人的尸检样本(40例葡萄糖耐量正常,31例糖尿病前期患者和32例2型糖尿病患者),在死亡前5年内接受了75 g口服葡萄糖耐量试验,从2002年到2016年收集的尸检样本。使用Image Pro Plus软件定量β细胞面积分数(BCA)和α细胞面积。使用线性回归分析评估BCA和α细胞面积与葡萄糖耐量状态的关联,并估计血糖标志物和β细胞功能之间的斯皮尔曼相关系数。随着糖耐量状态的恶化,BCA的平均值显著降低(正常糖耐量组平均值±标准误1.85 ± 0.10%,糖尿病前期组平均值±标准误1.59 ± 0.11%,2型糖尿病组平均值±标准误1.17 ± 0.11%,趋势P < 0.001),而α-细胞面积和葡萄糖耐量状态之间没有显著关联。BCA与口服葡萄糖耐量试验和糖化血红蛋白测定中的空腹和2小时血糖水平呈负相关,与处置指数呈正相关(均P < 0.01)。结论:在日本人群中,从糖尿病前期阶段开始,随着糖耐量的恶化,β细胞质量显著下降。在葡萄糖耐受不良发生之前预防β细胞质量下降对于减轻2型糖尿病的负担很重要。
Aims/Introduction: Changes in histologically quantified beta- and alpha-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in beta- and alpha-cell mass according to the glucose tolerance status.Materials and Methods: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75-g oral glucose tolerance test within 5 years before death were selected from 643 community-based autopsy samples collected from 2002 to 2016. Fractional beta-cell area (BCA) and alpha-cell area were quantified with Image Pro Plus software. Associations of BCA and alpha-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and beta-cell function were estimated.Results: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean +/- standard error 1.85 +/- 0.10% in normal glucose tolerance, 1.59 +/- 0.11% in prediabetes and 1.17 +/- 0.11% in type 2 diabetes mellitus,Pfor trend < 0.001), whereas there was no significant association between alpha-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (allP < 0.01).Conclusions: beta-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining beta-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus.